4.7 Article

Siponimod Modulates the Reaction of Microglial Cells to Pro-Inflammatory Stimulation

Journal

Publisher

MDPI
DOI: 10.3390/ijms232113278

Keywords

sphingosine 1-phosphate receptor signalling; multiple sclerosis; neurodegeneration; modulation; polarization

Funding

  1. Novartis
  2. Christiane and Claudia Hempel Foundation
  3. James and Elisabeth Cloppenburg, Peek and Cloppenburg Dusseldorf Stiftung

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Siponimod, a modulator of S1PR, can selectively modulate the reaction of microglia in the central nervous system. It has the potential to be a treatment option for multiple sclerosis, as it can promote neurorepair while inhibiting autoimmune inflammation.
Siponimod (Mayzent (R)), a sphingosine 1-phosphate receptor (S1PR) modulator which prevents lymphocyte egress from lymphoid tissues, is approved for the treatment of relapsingremitting and active secondary progressive multiple sclerosis. It can cross the blood-brain barrier (BBB) and selectively binds to S1PR1 and S1PR5 expressed by several cell populations of the central nervous system (CNS) including microglia. In multiple sclerosis, microglia are a key CNS cell population moving back and forth in a continuum of beneficial and deleterious states. On the one hand, they can contribute to neurorepair by clearing myelin debris, which is a prerequisite for remyelination and neuroprotection. On the other hand, they also participate in autoimmune inflammation and axonal degeneration by producing pro-inflammatory cytokines and molecules. In this study, we demonstrate that siponimod can modulate the microglial reaction to lipopolysaccharideinduced pro-inflammatory activation.

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